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Safe dissipation hypothesis: glycation as an evolutionary force shaping human metabolism 安全耗散假说:糖基化是塑造人体代谢的进化力量
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-10 DOI: 10.1016/j.mehy.2025.111815
Flávio Furtado de Farias , Marcelo Coertjens
Why does the human body preferentially oxidize lipids over glucose at rest? Moving beyond energy-efficiency models, we propose an evolutionary explanation: this configuration may be an adaptation to minimize irreversible molecular damage from protein glycation. The Safe Dissipation Hypothesis (SDH) posits that basal lipid oxidation limits the accumulation of advanced glycation end-products (AGEs), which degrade slow-turnover proteins like collagen and crystallins. Metabolic evolution thus favored phenotypes that suppress unnecessary glycolytic flux, even at the cost of submaximal ATP yield. Supporting mechanisms include hepatic glucose buffering, upregulation of pyruvate dehydrogenase kinase 4 (PDK4), and enzymatic defenses like glyoxalase-1 (GLO1). We hypothesize that this architecture—shaped by ancestral intermittent food availability—underlies the metabolic mismatch behind modern hyperglycemia-related diseases. Predictions include lower collagen-AGEs in pre-agricultural remains and population-specific genetic signatures in pathways like GLO1 and PDK4. The SDH reframes aging and chronic disease as consequences of disrupted anti-glycation dynamics, intrinsically linking fuel preference to molecular preservation and longevity.
为什么人体在休息时优先氧化脂质而不是葡萄糖?超越能源效率模型,我们提出了一种进化解释:这种结构可能是一种适应,以尽量减少蛋白质糖基化造成的不可逆分子损伤。安全耗散假说(SDH)认为,基础脂质氧化限制了晚期糖基化终产物(AGEs)的积累,AGEs会降解胶原蛋白和结晶蛋白等慢代谢蛋白。因此,代谢进化倾向于抑制不必要的糖酵解通量的表型,即使以低于最大的ATP产量为代价。支持机制包括肝脏葡萄糖缓冲,丙酮酸脱氢酶激酶4 (PDK4)的上调和酶防御,如乙醛酶-1 (GLO1)。我们假设,这种由祖先的间歇性食物供应形成的结构,是现代高血糖相关疾病背后代谢不匹配的基础。预测包括农业前遗迹中胶原- ages较低,以及GLO1和PDK4等途径中特定人群的遗传特征。SDH将衰老和慢性疾病重新定义为被破坏的抗糖基化动力学的结果,将燃料偏好与分子保存和寿命内在地联系起来。
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引用次数: 0
Excess iron in food could indirectly affect lipid metabolism by affecting intestinal lithocholic acid levels: A scientific hypothesis 食物中过量的铁可以通过影响肠道胆石酸水平间接影响脂质代谢:一个科学假设
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-09 DOI: 10.1016/j.mehy.2025.111813
Zhe-Ying Jiang , Zi-Qi Zhu , Ying Wang , Wei-Jia Meng , Cui-Ping Li , Lian-Ping He , Xiang-Hu Wang
Lipid metabolism is crucial for cellular function and overall health. Dysregulation of lipid metabolism is associated with a variety of diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. Studies have shown that the gut microbiota can regulate the synthesis and transformation of bile acids, including Lithocholic acid (LCA). participates in the regulation of glucose, lipid, and drug metabolism by interacting with a variety of nuclear receptors, such as farnesoid X receptor, G-protein-coupled bile acid receptor, Vitamin D receptor, and pregnane X receptor. Recently, it has been discovered that regulating bile acid metabolism through LCA may provide a new strategy for managing lipid metabolism dysregulation. Excessive dietary iron has been proven to significantly affect the composition and diversity of the gut microbiota. Therefore, we hypothesize that dietary iron may indirectly affect lipid metabolism by influencing intestinal LCA levels.
脂质代谢对细胞功能和整体健康至关重要。脂质代谢失调与多种疾病有关,包括肥胖、糖尿病、心血管疾病和神经退行性疾病。研究表明,肠道菌群可以调节胆汁酸的合成和转化,包括石胆酸(LCA)。通过与多种核受体相互作用,参与糖、脂和药物代谢的调节,如法内甾体X受体、g蛋白偶联胆汁酸受体、维生素D受体和孕激素X受体。近年来,研究发现通过LCA调节胆汁酸代谢可能为控制脂质代谢失调提供一种新的策略。饮食中过量的铁已被证明会显著影响肠道微生物群的组成和多样性。因此,我们假设膳食铁可能通过影响肠道LCA水平间接影响脂质代谢。
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引用次数: 0
Enhancing the effects of mindfulness in migraine patients through transcranial magnetic stimulation: A plausible hypothesis 通过经颅磁刺激增强偏头痛患者正念的效果:一个似是而非的假设
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-08 DOI: 10.1016/j.mehy.2025.111808
Fernanda Moura Vargas Dias , Carolina Fiorin Anhoque , Christian Nogueira de Barros , Renata Goltara Liboni Vescovi , Fernando Zanela da Silva Arêas
Migraine is a prevalent neurovascular disorder marked by cortical hyperexcitability, trigeminovascular activation, and central sensitization. While pharmacological therapies are available, many patients exhibit partial responses or intolerable side effects. We hypothesize that combining repetitive transcranial magnetic stimulation (rTMS) with mindfulness-based interventions (MBIs) may offer a synergistic, non-pharmacological approach to migraine management. rTMS, particularly when applied over the dorsolateral prefrontal cortex (DLPFC), has shown promise in modulating cortical excitability and reducing migraine frequency. Concurrently, mindfulness practices have demonstrated neurophysiological effects—including enhanced frontal cortical inhibition, increased alpha wave activity, and reduced limbic reactivity—that parallel rTMS-induced changes. Both interventions influence key regions implicated in pain perception and emotional regulation, suggesting overlapping mechanisms. We propose that mindfulness may act as a neurocognitive enhancer of rTMS-induced plasticity, while rTMS may acutely normalize dysfunctional cortical dynamics, facilitating a deeper engagement in mindfulness practice. This dual modulation could target both the physiological and psychological components of migraine, producing sustained therapeutic effects. Preliminary clinical data in other populations support greater efficacy when rTMS and mindfulness are combined, though this has not yet been systematically explored in migraine. We call for mechanistically informed, controlled studies to evaluate this hypothesis and to define optimal timing, dosing, and patient selection criteria. If validated, this integrative model may represent a novel treatment paradigm for individuals with refractory migraine.
偏头痛是一种普遍的神经血管疾病,其特征是皮质亢进、三叉神经血管激活和中枢致敏。虽然药物治疗是可用的,但许多患者表现出部分反应或无法忍受的副作用。我们假设将重复经颅磁刺激(rTMS)与正念干预(mbi)相结合可能为偏头痛治疗提供一种协同的非药物方法。rTMS,特别是应用于背外侧前额叶皮质(DLPFC)时,在调节皮质兴奋性和减少偏头痛频率方面显示出希望。同时,正念练习已经证明了神经生理效应——包括增强额叶皮质抑制,增加α波活动,减少边缘反应——与rtms引起的变化相似。这两种干预都影响涉及疼痛感知和情绪调节的关键区域,表明机制重叠。我们认为,正念可能是rTMS诱导的可塑性的神经认知增强剂,而rTMS可能会使功能失调的皮质动力学急剧正常化,促进更深入的正念练习。这种双重调节可以针对偏头痛的生理和心理成分,产生持续的治疗效果。其他人群的初步临床数据支持当rTMS和正念相结合时更有效,尽管这还没有在偏头痛中系统地探索。我们呼吁进行机械信息、对照研究来评估这一假设,并确定最佳时间、给药和患者选择标准。如果得到验证,这种综合模型可能为难治性偏头痛患者提供一种新的治疗范例。
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引用次数: 0
Ecotones—inter-biome transition zones—the wombs of both evolution and cancer 过渡带——生物群系间的过渡地带——是进化和癌症的摇篮
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-04 DOI: 10.1016/j.mehy.2025.111809
Ofer N. Gofrit , Tzahi Neuman
An ecotone is a concept in ecology that refers to a transition zone between two biomes such as forest–grassland. The exposure to environmental gradients induces physiological stress on bordering biotas leading to high genetic diversity, high mutation rate, and intensified selection pressures. We hypothesized that similar forces act on interfaces between epithelia, that these transitions zones can be viewed as ecotones, and that cancer develops in these sites. Examples are: carcinoma of the larynx most commonly developing in the ecotone between the squamous stratified epithelium of the upper glottis and the pseudo-stratified epithelium of the lower glottis, esophageal adenocarcinoma develops in the ecotone between the stratified squamous epithelium of the esophagus and the simple columnar stomach epithelium, anal cancer develops at the ecotone between the squamous stratified epithelium of the anoderm and the columnar epithelium of the rectum, and uterine cervix cancer that almost always develops in the ‘transformation zone’, an ecotone between the ectocervix (squamous epithelium) and endocervix (columnar epithelium). If the hypothesis is correct, surgically created ecotones should also be prone to cancer development. Indeed, the risk of cancer is increased after uretero-sigmoidostomy, ileal-bladder augmentation, and gastric bypass. The physical and chemical gradients of ecotones disrupt mucosal architecture and expose vulnerable basal cells to carcinogens. The implications of ecotones modifying surgery should be borne in mind during post-operative follow-up and when planning new surgeries. Study of the ecotone concept can elucidate and predict mechanisms in oncology and potentially also in other medical fields.
过渡带是生态学中的一个概念,指的是两个生物群落(如森林-草地)之间的过渡地带。暴露于环境梯度下会对边缘生物产生生理应激,导致高遗传多样性、高突变率和加剧的选择压力。我们假设类似的力作用于上皮之间的界面,这些过渡区可以被视为过渡带,并且癌症在这些部位发展。例子有:喉癌最常发生在上声门鳞状层状上皮和下声门假层状上皮之间的过渡带中,食管腺癌发生在食管鳞状上皮和单纯柱状胃上皮之间的过渡带中,肛门癌发生在肛肠鳞状层状上皮和直肠柱状上皮之间的过渡带中。宫颈癌几乎总是发生在“转化区”,即子宫颈外(鳞状上皮)和子宫颈内(柱状上皮)之间的过渡带。如果这一假设是正确的,那么通过手术产生的过渡性基因也应该容易患上癌症。事实上,在输尿管-乙状结肠造口术、回肠-膀胱扩张术和胃旁路术后,癌症的风险增加了。交错体的物理和化学梯度破坏粘膜结构,使脆弱的基底细胞暴露于致癌物。在术后随访和计划新手术时,应牢记改良手术的意义。对ecotone概念的研究可以阐明和预测肿瘤的机制,也可能用于其他医学领域。
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引用次数: 0
Subclinical mastitis during lactation: A modifiable risk factor for breast cancer? 哺乳期亚临床乳腺炎:乳腺癌的可改变危险因素?
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-02 DOI: 10.1016/j.mehy.2025.111810
Sallie S. Schneider , Brian T. Pentecost , Ashley R. Banas , Aliyah Dalier , Vignesh Narayanaswamy , Emma C. Gotschlich , Kathleen F. Arcaro
Chronic inflammation likely contributes to breast cancer risk, but epidemiologic studies are inconclusive. Two types of inflammatory episodes in breast tissue, referred to here as clinical mastitis and subclinical mastitis, have received little to no attention as risk factors for breast cancer. Clinical mastitis represents an acute painful inflammatory state of the breast that in most cases will be quickly treated and resolved. In contrast, subclinical mastitis remains undetected in most cases and may represent chronic inflammation. Based on the concentration of sodium (Na) and cytokines in milk, several publications suggest that subclinical mastitis is relatively common and can persist for extended periods. We propose that subclinical mastitis is a modifiable risk factor for breast cancer. This chronic subclinical inflammatory profile in breast tissue may cause genetic instability and perturb epigenetic mechanisms leading to cancer. We suggest studies to determine the extent that subclinical mastitis is associated with breast cancer risk.
慢性炎症可能会增加患乳腺癌的风险,但流行病学研究尚无定论。乳腺组织中两种类型的炎症发作,在这里被称为临床乳腺炎和亚临床乳腺炎,作为乳腺癌的危险因素很少或没有得到关注。临床乳腺炎表现为乳房的急性疼痛炎症状态,在大多数情况下会很快得到治疗和解决。相比之下,亚临床乳腺炎在大多数情况下仍未被发现,可能代表慢性炎症。根据牛奶中钠(Na)和细胞因子的浓度,一些出版物表明,亚临床乳腺炎相对常见,并可持续较长时间。我们认为,亚临床乳腺炎是乳腺癌的一个可改变的危险因素。乳腺组织的这种慢性亚临床炎症可能导致遗传不稳定和扰乱表观遗传机制,从而导致癌症。我们建议进行研究,以确定亚临床乳腺炎与乳腺癌风险相关的程度。
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引用次数: 0
Integration of parenteral nutrition with galactose may improve neurodevelopmental outcomes for preterm newborns 肠外营养与半乳糖的整合可能改善早产新生儿的神经发育结局
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-29 DOI: 10.1016/j.mehy.2025.111807
Isabella Panfoli
Although 90 % of premature babies survive, there is still a need for interventions to improve motor and cognitive neurodevelopmental outcomes. Breast milk is the universally preferred nutrition for the newborn human infant for its numerous benefits. However, premature newborns, especially extremely preterm (below 28 weeks gestational age), do not have access to milk. Those infants often experience severe illness due to the immaturity of multiple systems, needing parenteral nutrition for the first days in the neonatal intensive care unit. Notably, premature breast milk adjusts to the changing needs of the premature for the lactose and protein content. For those babies that cannot be fed maternal milk due to the prematurity of multiple systems, parenteral nutrition is tailored to mimic a pre-birth condition in that it only delivers dextrose as the carbohydrate source. This paper challenges the notion that premature newborns should be considered as though they had not yet been born. It proposes the hypothesis that early supplementation of parenteral nutrition with galactose—emulating the composition of maternal milk—may help mitigate complications associated with premature brain development. Galactose plays a pivotal role in myelination linked to cognitive development. Controlled clinical and animal model trials are proposed to support the hypothesis that the use of breast milk-like parenteral nutrition can prevent neonatal hypoglycemia while improving neurodevelopment in extremely premature newborns.
虽然90%的早产儿存活了下来,但仍然需要干预措施来改善运动和认知神经发育的结果。母乳是人类新生儿普遍首选的营养,因为它有许多好处。然而,早产新生儿,特别是极度早产儿(小于28周胎龄),无法获得母乳。由于多系统的不成熟,这些婴儿往往会经历严重的疾病,在新生儿重症监护病房的头几天需要肠外营养。值得注意的是,早产母乳会根据早产儿对乳糖和蛋白质含量不断变化的需求进行调整。对于那些由于多系统早产而不能喂养母乳的婴儿,肠外营养是为了模仿出生前的情况而量身定制的,因为它只提供葡萄糖作为碳水化合物来源。这篇论文挑战了早产儿应该被认为是好像他们还没有出生的观念。它提出了一种假设,即早期补充半乳糖肠外营养-模仿母乳的成分-可能有助于减轻与大脑过早发育相关的并发症。半乳糖在与认知发育相关的髓鞘形成中起着关键作用。我们提出了对照临床和动物模型试验,以支持使用母乳样肠外营养可以预防新生儿低血糖,同时改善极早产儿神经发育的假设。
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引用次数: 0
Parkinson’s disease as a superposition of wake and sleep states: a hypothesis of vicious cycle neurodegeneration 帕金森病是清醒和睡眠状态的叠加:恶性循环神经退化的假设
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-26 DOI: 10.1016/j.mehy.2025.111796
Graeme Greenup
Current models of Parkinson’s disease (PD) emphasize dopaminergic deficits and α-synuclein pathology but struggle to account for its heterogeneous symptoms and progression. This paper proposes PD as a disorder of failed sleep–wake state separation, manifesting as a pathological superposition of REM-like and wake-like brain states. Here, “superposition” refers to the co-presence of incompatible neural programs—REM-associated motor suppression, dream-like cognition, and autonomic dysregulation persisting into wakefulness, and wake-like activity intruding into sleep. This hybrid state disrupts neural boundaries, generating motor and non-motor symptoms through conflicting physiological processes. In humans, sustained cortical overdrive (COD)—high-level cerebral activation that interferes with subcortical sleep–wake circuits—initiates and perpetuates this mixing through a primary vicious circle. A secondary loop involving impaired glymphatic clearance and neuroinflammation accelerates neurodegeneration, which in turn further erodes state boundaries. The model unifies PD symptomatology under a single pathophysiological process, suggests interventions targeting sleep–wake restoration, and offers testable predictions for research with possible extension to other neurodegenerative conditions. It reframes Parkinson’s disease as a measurable, modifiable failure of brain-state regulation—challenging researchers to treat sleep–wake boundary collapse with the same urgency as dopamine loss.
目前的帕金森病(PD)模型强调多巴胺能缺陷和α-突触核蛋白病理,但难以解释其异质性症状和进展。本文认为PD是一种睡眠-清醒状态分离失败的障碍,表现为rem样脑状态和清醒样脑状态的病理叠加。在这里,“叠加”是指不相容的神经程序共同存在——快速眼动相关的运动抑制、梦样认知和持续到清醒状态的自主神经失调,以及清醒样活动侵入睡眠。这种混合状态破坏了神经边界,通过相互冲突的生理过程产生运动和非运动症状。在人类中,持续的皮层过度驱动(COD)——干扰皮层下睡眠-觉醒回路的高水平大脑激活——通过主要的恶性循环引发并延续了这种混合。次级循环涉及受损的淋巴清除和神经炎症加速神经退行性变,进而进一步侵蚀状态边界。该模型统一了PD在单一病理生理过程下的症状,提出了针对睡眠-觉醒恢复的干预措施,并为可能扩展到其他神经退行性疾病的研究提供了可测试的预测。它将帕金森氏症重新定义为一种可测量的、可改变的大脑状态调节失败,这对研究人员提出了挑战,要求他们像治疗多巴胺丢失一样紧迫地治疗睡眠-觉醒边界崩溃。
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引用次数: 0
A multilayer ‘tension-reset’ hypothesis: Acupuncture’s distant effects via biotensegrity across skin–fascia–muscle layers 多层“张力重置”假说:针刺通过皮肤筋膜-肌肉层的生物张力完整性产生的远距离效应
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-26 DOI: 10.1016/j.mehy.2025.111797
Yoshito Mukaino , Masahiko Mukaino
While evidence supports the therapeutic effects of acupuncture, particularly for analgesia, the mechanism for its distant effects remains debated. Conventional neurobiological theories, while valid, do not fully account for the rapid, systemic, and meridian-specific responses seen in clinical practice. This paper proposes a ’tension-reset’ hypothesis based on biotensegrity, positing that the interconnected skin-fascia-muscle complex functions as a multilayered tensional network. We hypothesize that acupuncture needling induces a local ’tension reset’ within this complex through mechanisms such as fascial remodeling, altered hyaluronan fluidity, a dermal ’tension switch,’ and neurogenic muscle relaxation. This localized change in mechanical tension is then rapidly propagated throughout the body-wide tensegrity system via mechanotransduction. We propose that these pathways of force transmission are the anatomical correlates of traditional acupuncture meridians. This model is consistent with clinical observations such as reduced tissue stiffness measured by elastography and the clinical efficacy of tension-based diagnostic and treatment approaches. By framing meridians as biomechanical pathways, this tensegrity-based hypothesis offers a testable framework that bridges Eastern medical concepts with Western science, potentially unifying our understanding of acupuncture and other manual therapies while providing a basis for refining clinical techniques.
虽然有证据支持针灸的治疗效果,特别是镇痛效果,但其远期效果的机制仍存在争议。传统的神经生物学理论虽然有效,但并不能完全解释临床实践中所见的快速、系统和经络特异性反应。本文提出了一种基于生物张力完整性的“张力重置”假设,假设相互连接的皮肤筋膜-肌肉复合体作为多层张力网络发挥作用。我们假设,针刺通过筋膜重塑、透明质酸流动性改变、皮肤“张力开关”和神经源性肌肉放松等机制,在该复合体中诱导局部“张力重置”。这种局部的机械张力变化随后通过机械传导迅速传播到整个体张拉整体系统。我们认为这些力的传递途径是传统针灸经络的解剖关联。该模型与临床观察结果一致,如弹性成像测量的组织刚度降低以及基于张力的诊断和治疗方法的临床疗效。通过将经络作为生物力学途径,这种基于张力整体的假设提供了一个可测试的框架,将东方医学概念与西方科学联系起来,有可能统一我们对针灸和其他手工疗法的理解,同时为完善临床技术提供基础。
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引用次数: 0
Decellularization of urinary bladder autograft in the treatment of bladder cancer 自体膀胱脱细胞移植治疗膀胱癌
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-25 DOI: 10.1016/j.mehy.2025.111795
Michał C. Czarnogórski , Layla Settaf-Cherif, Tomasz Drewa, Jan Adamowicz
Despite the unprecedented progress in urological treatment of both benign and malignant bladder conditions, considerable proportion of patients still develop end-stage bladder failure that will eventually require cystectomy. The majority of cystectomies is performed due to bladder cancer. Radical cystectomy with urinary diversion utilizing bowel segments is at present a gold standard, yet it is associated with considerable metabolic complications. With the advent of urinary bladder transplantation research, the new hope emerged for well-informed individuals who would like to preserve natural way of voiding. The vascularized composite bladder allograft transplantation was proven technically and clinically feasible, although for now the indications include only benign bladder conditions, due to the considerable recurrence rate of bladder cancer. We propose hypothetical therapeutic option for non-muscle invasive bladder cancer patients, namely urinary bladder autotransplantation, with blader mucosa decellularization, and subsequent cell seeding with recipients own urothelial progenitor cells. Theoretically, the patient would not require immunosuppressive agents, and would retain natural way of voiding, thus avoiding repeated transurethral bladder tumor resections, BCG instillations, and maintaining high quality of life.
尽管泌尿外科对良性和恶性膀胱疾病的治疗取得了前所未有的进展,但仍有相当比例的患者发展为终末期膀胱功能衰竭,最终需要膀胱切除术。大多数膀胱切除术是由于膀胱癌。根治性膀胱切除术结合肠段导尿是目前的金标准,但它与相当大的代谢并发症相关。随着膀胱移植研究的出现,对于那些想要保留自然排尿方式的知情人士来说,新的希望出现了。带血管的复合异体膀胱移植在技术和临床上都是可行的,但由于膀胱癌的高复发率,目前的适应症仅包括膀胱良性状况。我们为非肌肉浸润性膀胱癌患者提出假设的治疗方案,即膀胱自体移植,膀胱粘膜脱细胞,然后用受体自身的尿上皮祖细胞播种细胞。理论上,患者不需要免疫抑制剂,保留自然排尿方式,避免反复经尿道膀胱肿瘤切除和卡介苗注射,维持高生活质量。
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引用次数: 0
Sleep-induced hypogonadism: A unifying hypothesis linking BPH, OSA, and low testosterone 睡眠诱发性腺功能减退:BPH、OSA和低睾酮之间的统一假说
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-23 DOI: 10.1016/j.mehy.2025.111793
Yu-Hsiang Lin , Po-Ting Lin , Kuo-Jen Lin , Tzu-Chi Teng , Yu-Ting Chen , Chen-Pang Hou , Jau-Yuan Chen , Chien-Lun Chen
The age-related decline in testosterone, often termed ’andropause,’ is traditionally viewed as an inevitable consequence of aging. However, emerging evidence suggests this decline is more closely associated with accumulating comorbidities than with age itself. We propose a unifying hypothesis of ’sleep disruption-induced hypogonadism,’ an acquired and potentially reversible condition driven by common age-related pathologies such as benign prostatic hyperplasia (BPH), obstructive sleep apnea (OSA), and chronic pain. These conditions precipitate a vicious cycle where symptoms like nocturia cause chronic sleep fragmentation and circadian dysregulation. This, in turn, suppresses the hypothalamic-pituitary–gonadal (HPG) axis, leading to reduced endogenous testosterone. This hypothesis is supported by extensive correlational data linking sleep disorders to low testosterone and, more compellingly, by interventional studies demonstrating that treatment of underlying sleep disruptors—such as BPH surgery or nocturia medication—can significantly restore testosterone levels. This framework also resolves the paradox of why CPAP therapy often fails to raise testosterone by highlighting the powerful confounding role of obesity. The primary implication of this hypothesis is a proposed paradigm shift in clinical practice: from a focus on hormone replacement to a ’sleep-centric,’ cause-oriented approach. We advocate that the diagnostic workup for low testosterone in aging men should include a primary assessment for and treatment of underlying sleep disorders before considering testosterone replacement therapy, fostering a more integrated, multidisciplinary management strategy.
与年龄相关的睾丸激素下降,通常被称为“男性更年期”,传统上被认为是衰老的必然结果。然而,新出现的证据表明,这种下降与累积的合并症密切相关,而不是与年龄本身有关。我们提出了一个“睡眠中断诱发性腺功能减退”的统一假设,这是一种由常见的与年龄相关的病理(如良性前列腺增生(BPH)、阻塞性睡眠呼吸暂停(OSA)和慢性疼痛)驱动的获得性和潜在可逆性疾病。这些情况引发了一个恶性循环,夜尿症等症状导致慢性睡眠碎片和昼夜节律失调。这反过来又抑制了下丘脑-垂体-性腺(HPG)轴,导致内源性睾酮减少。这一假设得到了大量相关数据的支持,这些数据将睡眠障碍与低睾丸激素联系在一起,更令人信服的是,干预性研究表明,治疗潜在的睡眠干扰因素——如前列腺增生手术或夜尿药物——可以显著恢复睾丸激素水平。这个框架也解决了为什么CPAP治疗经常不能提高睾丸激素的悖论,因为它强调了肥胖的强大混淆作用。这一假设的主要含义是在临床实践中提出的范式转变:从关注激素替代到“以睡眠为中心”,以原因为导向的方法。我们主张,在考虑睾酮替代疗法之前,老年男性低睾酮的诊断检查应包括对潜在睡眠障碍的初步评估和治疗,促进更综合的多学科管理策略。
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引用次数: 0
期刊
Medical hypotheses
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